The Role of Triglyceride-Rich Lipoprotein Families in the Progression of Atherosclerotic Lesions as Determined by Sequential Coronary Angiography From a Controlled Clinical Trial

Abstract

Abstract We have demonstrated previously in a subset of Monitored Atherosclerosis Regression Study (MARS) subjects with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease that lovastatin significantly reduces cholesterol-rich lipoprotein B (LpB) but has little effect on complex, triglyceride-rich apolipoprotein (apo) B–containing LpB c (the sum of LpB:C, LpB:C:E and LpA-II:B:C:D:E) particles defined by their apolipoprotein composition. This differential effect of lovastatin on apoB-containing lipoprotein families offered the opportunity to determine in the same subset of MARS subjects the independent relationship of LpB and LpB c with the progression of coronary artery disease. Subjects randomized to either lovastatin (40 mg twice daily) or matching placebo were evaluated by coronary angiography before randomization and after 2 years of treatment, and the overall coronary status was judged by a coronary global change score. In the lovastatin-treated group, there were 22 nonprogressors (69%) and 10 progressors (31%), while in the placebo group 13 subjects (42%) were nonprogressors and 18 (58%) were progressors ( P <.03). In the lovastatin-treated group, lipid and lipoprotein parameters did not differ between progressors and nonprogressors except for LpB c and LpA-II:B:C:D:E particle levels, which were statistically higher in progressors ( P =.02). In the placebo-treated group, progressors differed from nonprogressors by having significantly higher levels of triglycerides ( P =.03) and apoC-III in VLDL+LDL ( P =.05), the characteristic constituents of triglyceride-rich lipoproteins. In the placebo- and lovastatin-treated groups combined, progressors had significantly higher on-trial levels of triglycerides ( P =.003), VLDL cholesterol ( P =.005), apoC-III in VLDL+LDL ( P =.008), apoC-III ( P =.01), apoB ( P =.03), and total cholesterol ( P =.04) than nonprogressors. Even after adjustment for treatment group, progressors in the combined placebo- and lovastatin-treated groups had significantly higher levels of LpB c , LpA-II:B:C:D:E, triglycerides, and apoC-III in VLDL+LDL than nonprogressors. Progressors in the placebo-treated, lovastatin-treated, and combined treatment groups had lower levels of LpA-I but not LpA-I:A-II than nonprogressors, and this difference reached statistical significance ( P =.047) in the combined sample adjusted for treatment group. Results of this study show that elevated levels of triglyceride-rich LpB c in general and LpA-II:B:C:D:E in particular contribute significantly to the progression of coronary artery disease. Furthermore, they provide additional evidence for the potentially protective role of LpA-I particles in the atherogenic process and suggest that apolipoprotein-defined lipoprotein families may be more specific prognosticators of coronary artery atherosclerosis progression than lipids and apolipoproteins.